The cause of elevated infection rates and the reduced response to antigens in patients with multiple myeloma and in mice with plasmacytomas has not been elucidated. The ultimate objective of this project is to determine the mechanism by which malignant plasma cell tumors suppress the immune response. Three experimental approaches are planned: 1) Experiments will be performed to determine whether the immune deficit in plasmacytoma-bearing mice resides in the B or T cell populations; this will be studied using a hapten-carrier system where B and T cell functions are easily dissected. (2) Soluble immunodepressive factors have been proposed to explain the immunodepression in plasmacytoma-bearing animals and in animals displaying tolerance and antigenic competition. Millipore diffusion chambers contaning normal lymphoid cells and antigen will be used to test for the presence of such factors in tumor-bearing and tolerant mice as well as in animals undergoing an immune response to a heterologous antigen. In vitro, this hypothesis will be tested using parabiotic tissue culture chambers with normal spleen cells and antigen separated by Millipore filters from tumor or tolerant cells or cells producing antibody to a heterologous antigen. 3) Immunosuppression will also be studied at the level of IgM synthesis by determining the effect of malignant plasma cells on IgM production by normal mouse spleen cells when the two populations are grown together in short-term tissue culture.